Adrenal Gland Physiology Flashcards
Key Steps in steroid hormone biosynthesis
- release of cholesterol from lipid droplets inside the cell by removing esters
- Subsequent steps in steroid hormone synthesis occur within either the mitochondria or endoplasmic reticulum.
- The rate-limiting step requires mitochondrial enzymes - the cytochrome P-450 enzymes or 20, 22 desmolase.
- Pregnenolone is the product of this reaction. This rxn occurs throughout the cortex.
- each pathway used different biosynthetic enzymes. .
Transport of glucocorticoids in plasma
- Cortisol circulates primarily (90%) bound to proteins.
- Of the 90% that is bound, 75% is bound to cortisol binding globulin (CBG) and 15% is bound to albumin.
- 10% circulates in a free form. Remember, free hormone is the amount that matters physiologically and is regulated.
General/overall actions of cortisol
- Major stress hormone in the body, necessary for life. Prolonged stress is detrimental to health.
- Formed in the zona fasiculata
- Overall: ↓ insulin actions → ↑ serum glucose, ↑ FFA from adipose tissue
Cortisol action @ liver
↑ gluconeogenesis → ↑ serum glucose
Cortisol action @ adipose and muscle tissue
- Adipose Tissue:
- Activates hormone sensitive lipase → ↑ serum FFA
- Results in fat deposition on trunk, abdomen, face; mobilization of fat from extremities
- Muscle: proteolysis makes more amino acids available for gluconeogenisis
Cortisol effects on water balance
Inhibits ADH → ↑ water excretion (inverse stimulation of ADH secretion)
Cortisol actions @ stomach
Increased gastric acid secretion
Cortisol actions @ adrenal cortex
- Paracrine effect: Increases conversion of NE → Epi
- Cortisol is permissive of epinephrine; epi is much more active in presence of cortisol
Cortisol actions @ heart
- ↑ cortisol → ↑ RBC production → Polycythemia
- Too little cortisol → ↓ RBC production → Anemia
- ↑ β adrenergic receptor synthesis in target tissues, so for heart, ↑ HR, contractility, etc.
Cortisol actions @ brain
depression and psychotic symptoms result from changes in cortisol levels, mechanism unknown
Consequences of excess cortisol
- Skin: thinning by ↓ fibroblast proliferation
- Capillaries: fragility → bruising
- CV: polycythemia
- Bone: ↓ calcium absorption from gut and interferes with bone formation → fractures and osteoporosis
- Cortisol is antagonist of Vitamin D
- Anti-inflammatory effects: influences prostaglandins, cytokines, migration, etc. Inhibits phospholipase A2
- Immunosuppressant: ↓ T-cell proliferation, ↓ T-cell activation
Mechanism of ACTH release
- Parvocellular (small) neurons (Supraoptic + Paraventricular) from the hypothalamus secrete CRH into H-P portal system
- CRH binds to receptors on corticotrophs in the pituitary thereby activating adenylate cyclase
- Ca2+ influx which stimulates release of ACTH.
- POMC gene transcription is also activated.
Regulations of release of ACTH
- Negative feedback: Plasma free cortisol feeds back on the hypothalamus and the pituitary to inhibit CRH and ACTH secretion.
- Stimulation of release: Stress of various forms stimulates secretion of CRH and thus ACTH and cortisol.
- Stress can be physical in nature such as pain, trauma or cold exposure.
- Emotional stress and specific chemicals are also effective stimulants.
ACTH actions @ adrenal gland (general)
ACTH interacts with receptors on the cells of the Zona fasciculata and reticularis to promote secretion of cortisol. ACTH has several actions, which lead to increased cortisol secretion.
Actions of ACTH @ adrenal gland ==> cortisol secretion
- In the cortex, ACTH → ↑ cAMP levels (via Gs protein) → ↑ the rate of synthesis of pregnenolone.
- ↑ All cellular numbers in adrenal cortex, and ↑ in all enzymes
- ACTH mainly ==> cortisol, so mineralcorticoids still secreted if ACTH disrupted
- ↑ LDL uptake
- ↑ Hydrolysis of stored cholesterol esters and transport of cholesterol into mitochondria.
- Adrenal androgens generally vary with the secretion of cortisol and appear to be stimulated by ACTH.
